Estradiol negatively associates with metabolic dysfunction-associated steatotic liver disease in children.

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease in children and adolescents. Studies in adults indicate that MASLD is more prevalent in males compared to females and that sex hormones may play a significant role in MASLD development. However, limited pediatric research is available on the relation between sex hormones and MASLD. This study investigates associations between sex hormones and MASLD in children with overweight and obesity.

METHODS

A cross-sectional study was conducted in children with overweight and obesity in a tertiary care center (Maastricht UMC+). A comprehensive serum sex hormone panel, serum alanine aminotransferase (ALT) and hepatic steatosis on ultrasound (HS) were determined in 290 participants. Controlled Attenuation Parameter (CAP, measured with FibroScan) was available in 75 participants. Associations between sex hormones and MASLD parameters (ALT, HS and CAP) were investigated.

RESULTS

This study found that estradiol, Anti-Müllerian hormone (AMH) and sex hormone-binding globulin (SHBG) inversely associated with ALT (p=0.018, p=0.048 and p<0.001). Free (FT) and bioavailable (BT) testosterone and dehydroepiandrosterone sulfate (DHEAS) positively associated with ALT (both p=0.006). In addition to this, AMH and SHBG inversely associated with HS (p=0.028 and p<0.001), while FT, BioT and DHEAS positively associated with HS (p=0.024, p=0.024 and p=0.042). Lastly, AMH and SHBG inversely associated with CAP (p=0.04 and p<0.001), whereas follicle stimulating hormone, total testosterone (TT), FT, BioT, androstenedione and DHEAS positively associated (p=0.034, p=0.04, p=0.032, p=0.032, p=0.007 and p=0.003).

CONCLUSIONS

Estradiol, AMH and SHGB inversely associate with MASLD parameters, while androgens, including TT, FT, BioT, and DHEAS, positively associate with MASLD parameters in children with overweight and obesity.